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From Washington to Beijing. Ten Years Dream Trip of CNHUPO & HLPP. Fuchu He Consortium of CNHUPO Consortium of HLPP/CNHLPP State Key Laboratory of Proteomics. From 2002.4 to 2012.5. Outline. History Discovery Expectancy. Preview.
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From Washington to Beijing Ten Years Dream Trip of CNHUPO & HLPP Fuchu He Consortium of CNHUPO Consortium of HLPP/CNHLPP State Key Laboratory of Proteomics From 2002.4 to 2012.5
Outline • History • Discovery • Expectancy
Preview First papers of proteomics in international journal in 2001 First papers of proteomics in Chinese published in 1998 1995 Marc Wilkins 1998
Preview 2001.2 Human Genome Project opened a new era 1985-2000 2001.2 Feb. 16, 2001 Feb. 15, 2001 Turning point: from genome to proteome Proteomics in Genome-land And now for proteome
HUPO 1st Workshop & Planning Session (Washington, USA, 4.29-30, 2002) Review: Human Proteome Research in China Sparkplug: Scientific Goals/Roadmap of Human Proteome Project Human Liver Proteome Project Fuchu He, Qichang Qia, Siqi Liu, Qihong Sun, Rong Zeng, Xiaohang Zhao, Xiaohong Qian, Rong Wang, Ningzhi Xu, et al
Main Scientific Goals of Human Proteome Project (HPP) • Confirmation/annotation of predictive genes from Human Genome Project • Elucidation of global composition and regulation of proteome and discrimination with that of transcriptome • Set-up of protein linkage map (Sets, Assemblies, complexes or machines) & network. • Establishment of proteomic basis of physiology & pathology
Human Genome Project Genetic map Physical map Sequence map Milestone comparison Human Proteome Project • Expression profile • Modification profile • Interaction map • Localization map
Human Proteome Project Roadmap Human Genome Project
Dream Trip 2002.04 Washington Board interest in initiating HLPP
Dream Trip 2002.10 Beijing Fragrant Hill Meeting Getting consensus view for scientific objectives of HLPP
HUPO Liver Proteome Workshop Fragrant Hill Hotel Beijing, China October 22nd-24th, 2002 Photoed in 2002.10
Human Liver Proteome Project Fuchu He, Ph.D. Chinese Human Proteome Organization
Human Liver Proteome Project (HLPP) Why What How When Who ? ? ? ? ? wwwww.HLPP.HUPO
Bridging Liver Proteome with Liver Physiology & Pathology WITHIN HUMAN LIVER PROTEOME PROJECT Metabolome Toxicome Pharmacome Liver Proteome Hepatitisome Hepatomaome
BETWEEN HUMAN PROTEOME PROJECTS Bridging Liver Proteome Project & Plasma Proteome Project • As a secretory organ, the liver performs the crucial function of producing the majority of circulating plasma proteins. Liver transcriptome ? Liver proteome Plasma proteome
BEYOND HUMAN PROTEOME PROJECT Bridging Genome, Transcriptome & Proteome Human Genome Identification of hypothetic genes Liver Proteome Liver Transcriptome Comparison of Global Regulation Pattern
Dream Trip 2002.11 Versailles HLPPinitiated,three inaugural chairs of HLPP were elected
Human Proteome Initiatives HLPP HPPP
Human Liver Proteome Project Fuchu He, Ph.D. HUPO Liver Proteome Project Workshop Chinese Human Proteome Organization
VISION Target new approaches toward uncovering the complex physiological processes taking place in the liver Expand liver proteome to its “PHYSIOME” and “PATHOME” to dramatically accelerate the development of diagnostics, prevention and therapeutics towards its diseases Develop standard operating procedures (SOPs) for other HUPO Initiatives
HLPP—Modern Prometheus Myth Liver Prometheus Liver diseases Eagle HLPP Modern Heracles Heracles Liberate Prometheus Prometheus stole fire from the gods and gave it to mortals. Prometheus Bound
MISSION Pathome Specimen Bank Database Physiome Antibody Bank Scientific objectives: “Solar System”of Liver Proteome Project Localization Map Linkage Map Expression Profile Modification Profile ORFeome
France Christian Brechot Canada John Bergeron China Fuchu He
Dream Trip 2004.10 Beijing First HUPO Congress in Asia Systematic Analysis of Human Fetal Liver Proteome 2003.10 Montreal Proposals about Working Plan; Executive Chair of HLPP 2005.08 Munich Pilot Phase Plan and progress of HLPP
Dream Trip 2008.08 Amsterdam Parallel Analysis of Proteomic and Metabolic Profiles on NAFLD 2006.05 Beijing Data analysis of Human Expression Profiling 2006.10 Long Beach Expression Profiling French Liver, Chinese FetalLiver, Chinese Adult Liver 2006.05 Bilbao Solar System of HLPP 2007.10 Seoul Systematic Deciphering of Human Liver Proteome
Dream Trip 2009.09 Toronto PHOENIX The first insight into the human liver proteome 2010.09 Sydney CNHPP Press Conference 2011.09 Geneva CNHPP & C-HPP HLPP, demo of HPP
CNHUPO Press Conference 2010.9.21 Sydney, Australia Xiaohong Qian Fuchu He Fuxiang He Jun Qin China Pushes for the proteome Nature. 2010 Sep 23;467(7314):380 Announce the CNHPP project
Development of CNHUPO Proteomics Committee of The Chinese Society of Biochemistry and Molecular Biology The 1st Committee 2002.10 Fuchu He 2 Organizations Jianping Ding The 2nd Committee 2007.8 President: Fuchu He; General Secretary: Xiaohong Qian 43 labs/universities; 69members The 3rd Committee 2011.4 Honorary President: Fuchu He President: Pengyuan Yang; General Secretary: Ping Xu 87 labs/universities; 110members
Educations&Trainings Organized about 50 training lessons 2000 more students joined
Funding Number of Programs Supported by NSFC
Publication Proteome in China www.pubmed.com
Special Issues Proteomics 2006,V2 J Proteome Res 2010, V1
Timeline of CNHUPO 2004, Dalian 2012, AOHUPO 6th congress 2002,Beijing 2005,Changchun Proteomics 2006,V2 2009, Taizhou 2006,Xi’an 2008. 9 Shanghai 2010.9 Shanghai J Proteome Res 2010, V1 2011, Hangzhou 2010.5 Lijiang 2003, Changsha 2007, Guangzhou
Initiation (2004.11.16, Beijing) CNHLPP 2004-2006 Evaluation (2005.7.23, Changsha) Jamboree of data analysis of expression profile General Assembly(2006.1.5, Beijing)
Participants about 1800, Scientists from overseas over 1000 Human Proteome Initiatives 2nd Round-table Seminar (BPRC, 2005. 10.31) HUPO Conference held in Asia in the first time
Joining in Human Proteome Initiatives HAI Sweden PSI UK Xiaohong Qian ……. HPPP USA HGPI HLPP China Pengyuan Yang …… Japan Qihong Sun …… Yunping Zhu …… MRPP HBPP Germany Disease Biomarkers Initiatives Mouse Models of Human Disease Mammary Gland Proteome Initiative (MGPI) Proteome Biology of Stem Cells Initiative Human Proteotheque Initiative (HuPI) …… Canada Biao Chen; Chenggang Zhang ……
Outline • History • Discovery • Expectancy
A HUPO Test Sample Study All results of our lab were correct!! Nature Methods. 2009, 6(6), 423-30. 23 labs involved Results of 6 labs were all right.
First Proteome of a Human Organ J Proteome Res. 2010 Jan;9(1):79-94 J Proteome Res. 2010 Jan;9(1):50-8
First proteome of human organs http://dblep.hupo.org.cn http://liverbase.hupo.org.cn J Proteome Res. 2010, Jan.
Data utilization Data exchange Nat Biotech 2008; 26(2):164-7
Regular Distribution Patterns of Protein Abundance Evolution Conservation degree Origin time + + Protein abundance - + High Low Domain number Domain coverage Mass category Information category Structure Function Rules of Proteome Composition
Acetylation of metabolic enzymes— Universefor diverse liver metabolisms Fatty acid metabolism Glycolysis Glucogenesis TCA To TCA Science comment:Acetylation rivals with phosphrylation. Glycogen metabolism Urea cycle
Acetylation of metabolic enzymes— Universe from bacteria to human Rules of Proteome Regulation
Network of Human Liver Proteins Interaction Screen 5026 human liver proteins 2582 proteins and 3484 interactions Novel interactions: 92.9%
Liver specific expressed, phenotype and disease proteins are significantly enriched SIGNIFICANCE
Liver Phenotype Protein Network High ratio of liver phenotype proteins are linked together (92 proteins had a 9.6-fold greater chance to have a liver phenotype after gene knockout than random selected proteins).